(R^*,S^*)-3-(4-methoxy-phenyl)-5-oxiranyl-4,5-dihydro-isoxazole

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (R^*,S^*)-3-(4-methoxy-phenyl)-5-oxiranyl-4,5-dihydro-isoxazole
• 英文别名: (5R)-3-(4-methoxyphenyl)-5-[(2S)-oxiran-2-yl]-4,5-dihydro-1,2-oxazole
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: WVIAOSWOEKFCAX-NEPJUHHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R^*,S^*)-3-(4-methoxy-phenyl)-5-oxiranyl-4,5-dihydro-isoxazole 在 硫脲 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以100%的产率得到(R^*,S^*)-3-(4-methoxy-phenyl)-5-thiiranyl-4,5-dihydro-isoxazole
  参考文献：
  名称：

  Inhibition of the Antibacterial Target UDP-(3-O-acyl)-N-acetylglucosamine Deacetylase (LpxC):  Isoxazoline Zinc Amidase Inhibitors Bearing Diverse Metal Binding Groups

  摘要：

  UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc deacetylase (LpxC) is a zinc amidase that catalyzes the second step of lipid A biosynthesis in Gram negative bacteria. Known inhibitors of this enzyme are oxazolines incorporating a hydroxamic acid at the 4-position, which is believed to coordinate to the single essential zinc ion. A new structural class of inhibitors was designed to incorporate a more stable and more synthetically. versatile isoxazoline core. The synthetic versatility of the isoxazoline allowed for a broad study of metal binding. groups. Nine of 17 isoxazolines, each incorporating a different potential metal binding functional group, were found to exhibit enzyme inhibitory activity, including one that is more active than the corresponding hydroxamic acid. Additionally, a designed affinity label inhibits LpxC in a time-dependent manner.

  DOI：

  10.1021/jm020183v
• 作为产物：
  描述：

  N-hydroxy-4-methoxybenzenecarboximidoyl chloride 在 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 3.0h， 生成 (R^*,S^*)-3-(4-methoxy-phenyl)-5-oxiranyl-4,5-dihydro-isoxazole
  参考文献：
  名称：

  Conformationally restrained β-blocking oxime ethers. 2. Synthesis and β-adrenergic properties of diastereoisomeric anti and syn 2-(5′-(3′-aryl-substituted)isoxazolidinyl)-N-alkylethanolamines☆

  摘要：

  The diastereoisomeric 2-(5'-(3'-aryl)isoxazolidinyl) ethanolamines 1c-h-4c-h were synthesized as analogs of the corresponding P-blocking isoxazolines unsubstituted on the aromatic ring 1a-4a, with the aim of checking the effects on the adrenergic properties of the insertion of a methoxy group or a chlorine atom in the ortho, meta or para position of the phenyl ring of 1a-4a. The relative configurations of 1c-h-4c-h were assigned on the basis of their H-1-NMR spectral characteristics. The new isoxazolines 1c-h-4c-h were tested for their affinity towards beta(1)- and beta(2)-adrenoceptors by radioligand binding experiments; compounds showing the highest affinity were also assayed for their beta-adrenergic activity by functional tests on isolated preparations. The results showed that most of the new compounds (1c-h-4c-h) possess a slightly better capacity to interact with the beta-receptors, compared with the corresponding analogs unsubstituted on the phenyl ring (1a-4a), and that the substitution that leads to compounds with the best properties is the one with the chlorine atom. Quantum mechanical calculations carried out in order to look for possible correlations between the beta-adrenergic properties and the conformational and electronic characteristics induced by the presence of the substituents on the phenyl ring of compounds of types 1-4 do not suggest any reasonable explanation for the trend of the affinity data.

  DOI：

  10.1016/0223-5234(94)90108-2

文献信息

• Conformationally restrained β-blocking oxime ethers. 2. Synthesis and β-adrenergic properties of diastereoisomeric anti and syn 2-(5′-(3′-aryl-substituted)isoxazolidinyl)-N-alkylethanolamines☆
  作者：A BALSAMO、M BRESCHI、G CHIELLINI、A LUCACCHINI、M MACCHIA、A MARTINELLI、C MARTINI、C NARDINI、E ORLANDINI、F ROMAGNOLI

  DOI：10.1016/0223-5234(94)90108-2

  日期：——

  The diastereoisomeric 2-(5'-(3'-aryl)isoxazolidinyl) ethanolamines 1c-h-4c-h were synthesized as analogs of the corresponding P-blocking isoxazolines unsubstituted on the aromatic ring 1a-4a, with the aim of checking the effects on the adrenergic properties of the insertion of a methoxy group or a chlorine atom in the ortho, meta or para position of the phenyl ring of 1a-4a. The relative configurations of 1c-h-4c-h were assigned on the basis of their H-1-NMR spectral characteristics. The new isoxazolines 1c-h-4c-h were tested for their affinity towards beta(1)- and beta(2)-adrenoceptors by radioligand binding experiments; compounds showing the highest affinity were also assayed for their beta-adrenergic activity by functional tests on isolated preparations. The results showed that most of the new compounds (1c-h-4c-h) possess a slightly better capacity to interact with the beta-receptors, compared with the corresponding analogs unsubstituted on the phenyl ring (1a-4a), and that the substitution that leads to compounds with the best properties is the one with the chlorine atom. Quantum mechanical calculations carried out in order to look for possible correlations between the beta-adrenergic properties and the conformational and electronic characteristics induced by the presence of the substituents on the phenyl ring of compounds of types 1-4 do not suggest any reasonable explanation for the trend of the affinity data.
• Inhibition of the Antibacterial Target UDP-(3-<i>O</i>-acyl)-<i>N</i>-acetylglucosamine Deacetylase (LpxC):  Isoxazoline Zinc Amidase Inhibitors Bearing Diverse Metal Binding Groups
  作者：Michael C. Pirrung、L. Nathan Tumey、Christian R. H. Raetz、Jane E. Jackman、Karnem Snehalatha、Amanda L. McClerren、Carol A. Fierke、Stephanie L. Gantt、Kristin M. Rusche

  DOI：10.1021/jm020183v

  日期：2002.9.1

  UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc deacetylase (LpxC) is a zinc amidase that catalyzes the second step of lipid A biosynthesis in Gram negative bacteria. Known inhibitors of this enzyme are oxazolines incorporating a hydroxamic acid at the 4-position, which is believed to coordinate to the single essential zinc ion. A new structural class of inhibitors was designed to incorporate a more stable and more synthetically. versatile isoxazoline core. The synthetic versatility of the isoxazoline allowed for a broad study of metal binding. groups. Nine of 17 isoxazolines, each incorporating a different potential metal binding functional group, were found to exhibit enzyme inhibitory activity, including one that is more active than the corresponding hydroxamic acid. Additionally, a designed affinity label inhibits LpxC in a time-dependent manner.